A new line of investigation is the pathogenesis of the translocation (8;21) leukemia, responsible for 15% of all acute myeloid leukemia (AML). This translocation fuses a portion of the AML1 gene on chromosome 21 to the ETO gene on chromosome 8, creating a new protein product called AML1/ETO. In current work, the association of ETO with other nuclear proteins that regulate gene expression was studied using the yeast two-hybrid method. One of the clones identified in this manner was found to have significant homology to the murine nuclear receptor co-repressor (N-CoR), a member of a multi-protein complex that represses transcription through the enzymatic modification of histones. Thus, a novel human N-CoR, which binds to the ETO proto-oncoprotein, has been identified. Future studies will clarify the relationship between ETO and N-CoR and their role in leukemogenesis.